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A Phase III Randomized Trial Comparing Concurrent Chemotherapy-Radiotherapy with Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma

Theodore Robnett, MD
OncoLink Assistant Editor
Last Modified: May 20, 2000

Presenter: A.T. Chan
Affiliation: Chinese University Hospital of Hong Kong, and others.

Background:

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemoradiation. The intergroup trial 0099 (Al-Sarraf, et al) showed a significant difference in progression free survival and overall survival of 5-FU/cisplatin and radiation therapy versus radiation therapy alone.

The purpose of this study was to verify that chemoradiation was appropriate in areas where NPC is endemic.

Of note the low incidence of nasopharyngeal carcinoma in the United States compared to that in Asia as well as the differences in how histologies are distributed between endemic areas and the United States make such a study necessary.

Materials and Methods:

1. Patients were randomized to concurrent cisplatin 40 mg/m2 weekly with RT (CRT), up to 8 cycles, versus RT alone.
2. Eligibility: KPS > 80. TXN2-3 or N1 with LN >= 4 cm.
3. RT regimens were identical in both arms. Dose to the nasopharynx with external beam radiation therapy (EBRT) was 66 Gy, with 58 Gy given to the upper neck. Higher doses were given for parapharyngeal infiltration (an additional 20 Gy) and "residual nodes" (7.5 Gy). Intracavitary boost could also be given (24 Gy/3 fractions).
4. A brachytherapy boost dose was an option, and given starting 4 weeks into EBRT.

Results:

1. 348 patients were entered, 319 were eligible for analysis.
2. 79% of patients in the CRT arm received at least 4 cycles of chemotherapy. 45% received at least 6 cycles. 6 patients randomized to CRT refused chemotherapy.
3. 92% of patients had WHO grade II or III histologies.
4. There was one treatment related death, an aspiration pneumonia in the RT only arm.
5. Two-year progression-free survival was 77% in the CRT arm, and 67% in the RT alone arm. The actuarial PFS survival curves showed a trend favoring the CRT arm (p = 0.07). Note that these data are different than those printed in the proceedings abstract where the differences in outcome were significant.
6. On subgroup analysis, no difference in PFS between the two arms was seen in stages T1-
7. In stage T3 patients, PFS differences were significant (p < 0.05) favoring the CRT arm.

Authors' Conclusions

This is only the second phase III randomized trial for CRT in this disease. Differences between this trial and the intergroup trial include a difference in distribution of histologies. Less than 50% of patients in the intergroup trial had undifferentiated NPC. Also, the results of the intergroup trial had a very low PFS in the radiation alone arm. The results in the radiation only arm of the present study are comparable to those of other studies.

Clinical/Scientific Implications:

1. This trial demonstrates that CRT in this population of patients with nasopharyngeal carcinoma may improve progression free survival.
2. CRT as delivered in this regimen is well tolerated.